Delaying preterm labour
Once labour starts, it cannot be stopped. But if we can prevent preterm labour from starting, we can keep babies in the womb for longer, and improve their chances of survival and a life free from disability.
Cyclic adenosine monophosphate (cAMP)
Preterm labour has many causes. Historically, studies on preterm labour have not distinguished between different causes, creating confusing and often contradictory conclusions.
Borne’s initial focus was on characterising the distinct pathways involved in the different forms of preterm labour.
Our research looks at the processes and mechanisms responsible for initiating labour at the cell and tissue levels. Borne-funded scientists have focused on understanding the role of cyclic adenosine monophosphate (cAMP), a key intracellular messenger that regulates the onset of labour.
Borne's myometrial cAMP studies
Borne scientists and PhD students are studying the physiological changes behind labour – what turns a relaxed uterus into a powerful contractile muscle when labour starts?
PhD student Dr Alice Varley is working with leading cardiac scientist Prof Manuela Zaccolo at Oxford University.
They are working to establish whether a better understanding of the cAMP micro domain signalling in myometrial cells can improve our ability to harness the pro-relaxation effects of cAMP to prevent preterm labour.
PhD student Jonathan Li is the recipient of the Robert McAlpine Studentship Award. He is studying the changes in myometrial cell function that are triggered by cAMP signalling as the uterus transitions from quiescence to contractility.
Jonathan is collaborating with Dr Louis Muglia, co-director of the Perinatal Institute at Cincinnati Children’s Hospital Medical Centre. Dr Muglia has identified three mutations in the cAMP pathway associated with an increased risk of preterm labour. In this exciting collaboration, we are contributing our expertise on the cAMP pathway to design experiments to investigate how these mutations may affect uterine function and fetal growth.
Post-doctoral scientist Dr Pei Fong Lai is studying myometrial tissue samples to examine how cAMP and progesterone signalling regulate the onset of contractions, both individually and together.
We have a collaboration with Professor Sam Mesiano, from Case Reserve in Ohio. Prof Mesiano is most recognised for his work on the mechanism by which progesterone maintains uterine quiescence during pregnancy, and we are working together to understand how cAMP activity and effectors may interact with the progesterone receptor, altering its function to sustain pregnancy.
Dr Lai has also been consulting with Professor George Baillie, the Chair of Molecular Pharmacology at Glasgow University and the Dean for post-graduate research.
Professor Baillie is an expert on the inhibition of cAMP metabolism, particularly the role of phosphodiesterase, the mechanism through which aminophylline increases myometrial cAMP levels.
We are working together to identify novel cAMP agonists and to understand how cAMP works in the muscle of the womb.
Meet Borne PhD student, Dr Alice Varley
Alice has had a passion for science from a young age. After graduating in Medicine from the University of Bristol in 2014, she worked as a junior doctor in the Oxfordshire area.
Following her passion for science and research, she pursued a PhD which investigates the role of cAMP, a signalling molecule within cells, in regulating the mechanisms and pathways that affect labour.
ProgrAm: testing a new treatment to delay labour
There have been no new treatments to prevent premature labour in the last 50 years.
We believe we may have found one.
Borne scientists have been studying the effects of aminophylline, a cAMP agonist, in the laboratory to understand how it regulates myometrial contractions. Combined with progesterone, our hypothesis is that aminophylline can be an effective new treatment to delay the onset of preterm labour.
- In November 2017, we started a feasibility trial to assess whether women could tolerate this combination treatment.
- The trial involves recruiting 70 pregnant women who are considered “high risk” for preterm labour – this usually means women who have previously had a miscarriage or a premature baby.
- 35 of them receive the new treatment of progesterone + aminophylline while the control group receives progesterone only.
If successful, this could mean that we have found a new application for an existing, readily available drug to prevent premature birth, alongside progesterone.
Next phase: applying for funding for a clinical trial involving over 500 women, taking us one step closer to preventing babies from being born too soon.